White Matter Hyperintensity Volume and Amyloid-PET Synergistically Impact Memory Independent of Tau-PET in Older Adults Without Dementia.

BACKGROUND:Alzheimer's disease (AD) and cerebrovascular disease are common, co-existing pathologies in older adults. Whether the effects of cerebrovascular disease and AD biomarkers on cognition are additive or synergistic remains unclear. OBJECTIVE:To examine whether white matter hyperintensity (WMH) volume moderates the independent association between each AD biomarker and cognition. METHODS:In 586 older adults without dementia, linear regressions tested the interaction between amyloid-β (Aβ) positron emission tomography (PET) and WMH volume on cognition, independent of tau-PET. We also tested the interaction between tau-PET and WMH volume on cognition, independent of Aβ-PET. RESULTS:Adjusting for tau-PET, the quadratic effect of WMH interacted with Aβ-PET to impact memory. There was no interaction between either the linear or quadratic effect of WMH and Aβ-PET on executive function. There was no interaction between WMH volume and tau-PET on either cognitive measure. CONCLUSION:Results suggest that cerebrovascular lesions act synergistically with Aβ to affect memory, independent of tau, highlighting the importance of incorporating vascular pathology into biomarker assessment of AD.